Role of pharmacogenetics of drug-metabolizing enzymes in treating osteosarcoma

Abstract

Introduction: Drug-metabolizing enzymes (DMEs) biotransform several toxins and xenobiotics in both tumor and normal cells, resulting in either their detoxification or their activation. Since DMEs also metabolize several chemotherapeutic drugs, they can significantly influence tumor response to chemotherapy and susceptibility of normal tissues to collateral toxicity of anticancer treatments.

Areas covered: This review discusses the pharmacogenetics of DMEs involved in the metabolism of drugs which constitute the backbone of osteosarcoma (OS) chemotherapy, highlighting what is presently known for this tumor and their possible impact on the modulation of future treatment approaches.

Expert opinion: Achieving further insight into pharmacogenetic markers and biological determinants related to treatment response in OS may ultimately lead to individualized treatment regimens, based on a combination of genotype and tumor characteristics of each patient.

Keywords:

• collateral toxicity,
• drug-metabolizing enzymes
• drug resistance,
• genetic polymorphisms,
• osteosarcoma,
• tailored therapy

Acknowledgments

The authors would like to thank Dr Jan Koster (Academic Medical Center, University of Amsterdam, The Netherlands) for having developed the R2 bioinformatic tool and for his assistance in its use. They also thank professors Rogier Versteeg and Peter Van Sluis (Academic Medical Center, University of Amsterdam, The Netherlands) for the array profiling of the IOR-ITCC osteosarcoma tumor samples.

Declaration of interest

M Serra has received study grants from the Italian Association for Cancer Research and from the Italian Ministry of Health (5 x mille grants). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Notes

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